Mobola plum seed methanolic extracts exhibit mixed type inhibition of angiotensinⅠ-converting enzyme in vitro

Objective: To explore the possible inhibitory potentials and mechanism by Mobola plum(Parinari curatellifolia) seeds crude methanol(CE) and flavonoid-rich(FE) extracts on angiotensin-1-converting enzyme(ACE Ⅰ).Methods: The sensitivity and kinetic model of inhibition of CE and FE on ACE Ⅰ using N-[3-(2-furyl)-acryloyl]-Phe-Gly-Gly as enzyme substrate for ACE Ⅰ was evaluated by Michealis Menten approach. The inhibition mechanism was explored from Lineweaver–Burk model and IC_(50) was determined from Cheng–Prusoff empirical analysis.Results: The IC_(50) of CE and FE were 13.54 and 39.38 mg/m L, respectively. Both extracts exhibited mixed type inhibition with the inhibitory constant(K_i) of CE was between0.38 and 0.37 mg/m L while that of FE showed a two-fold increase(1.62 mg/mL and0.28 mg/mL). FE on ACE Ⅰ demonstrated positive cooperativity with a Hill's coefficient of1.89.Conclusions: The study reveals the superior ACE Ⅰ inhibitory potential of CE over FE and suggest that mixed inhibition pattern of the enzyme might be the underlying mechanism of antihypertensive activity.

Angiotensin Ⅱ type 1 receptor antagonist inhibits growth of human bladder cancer xenograft

AngiotensinⅡis known as a key biologically active peptide in rennin-angiotensin system, which regulates blood pressure, and angiotensinⅡtype 1 receptor (AT1R) antagonists are widely used as antihypertensive drugs. Since several human cancers have been reported to express AT1R, it is worthwhile to test whether AT1R antagonists

Discovery of pyrogallol thermal reaction products from a model process of roasting coffee beans as potentα-glucosidase inhibitors

The roasting process of pyrogallol,a polyphenol compound distributed in coffee beverages,significantly enhanced itsα-glucosidase inhibitory activity.In this study,a bioassay-guided isolation of the thermal reaction products of pyrogallol led to the identification of two potentα-glucosidase inhibitors,4-4′dimer of pyrogallol(4,4′-DP)and 4-5′dimer of pyrogallol(4,5′-DP).Theirα-glucosidase inhibitory activity was higher than that of pyrogallol,as evidenced by comparing the IC_(50)values(206.2±1.2μM for 4,4′-DP,187.6±2.6μM for 4,5′-DP,2660±60.1μM for pyrogallol).And the roasting products were more potentα-glucosidase inhibitors compared to acarbose(IC_(50)=695±12.7μM).Enzyme kinetics demonstrated that 4,4′-DP and 4,5′-DP inhibitedα-glucosidase in an uncompetitive and a non-competitive manner,respectively.Docking simulations revealed that the main interaction forces between these two compounds andα-glucosidase were hydrogen bonding and hydrophobic effect.These results suggested that a simple roasting process might increase theα-glucosidase inhibitory activity of pyrogallol-containing foods such as coffee beverages.

Degradation and detoxification of microcystin-LR in drinking water by sequential use of UV and ozone

Microcystins （MCs） produced by cyanobacteria are strong hepatotoxins and classified as possible carcinogens. MCs pose a considerable threat to human health through tainted drinking and surface waters. Herein filtrated water from a waterworks in Harbin, China, was spiked with microcysfin-LR （MC-LR） extracted from a toxic scum of microcystis aeruginosa, and the spiked sample waters were treated using UV irradiation with consequent ozonation process （UV/O3）, compared with ozonation at a dose range commonly applied in water treatment plants, UV irradiation at 254 nm and UV irradiation combined with ozonation （UV＋O3）, respectively. The remaining of toxins were analyzed using high-performance liquid chromatography and also determined using a protein phosphatase type 2A inhibition assay, which was utilized to evaluate the reduction in toxicity. Results indicated that in comparison to other three processes （O3, UV, and UV＋O3）, UV/O3 process could effectively decrease both the concentration and toxicity of MC-LR at 100 μg/L level after 5 min UV irradiation with consequent 5 min ozonation at 0.2 mg/L （below 1 μg/L ）, while 0.5 mg/L ozone dose was required for the level below 0.1 μg/L. The addition of an UV treatment step to the existing treatment train may induce significant transformation of micropollutants and breaks down the natural organic matters into moieties unfavorable for ozone decomposition, stabilizing the ozone residual. These findings suggested that sequential use of UV and ozone may be a suitable method for the removal of these potentially hazardous microcystins from drinking water.